A pharmacokinetic study comparing single and repeated oral doses of 20�mg and 40�mg omeprazole and its two optical isomers, S-omeprazole (esomeprazole) and R-omeprazole, in healthy subjects

Hassan-Alin, Mohammed; Andersson, Tommy; Niazi, Mohammad; Röhss, Kerstin

doi:10.1007/s00228-004-0841-1

Cited by 83 publications

(80 citation statements)

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“…CYP2C19 and CYP3A4 are associated with the metabolism of esomeprazole in people, and CYP1A1/2 and CYP2D15 are associated in dogs 3, 24. Repeated PO administration of esomeprazole has been shown in human studies to result in an increase in its plasma concentration because of the inhibition of CYP2C19 3.…”

Section: Discussionmentioning

confidence: 99%

“…Repeated PO administration of esomeprazole has been shown in human studies to result in an increase in its plasma concentration because of the inhibition of CYP2C19 3. One study reported that the AUC of repeated PO doses was 2.4‐fold higher than that of a single 40 mg PO dose,3 suggesting that an accumulation of esomeprazole is expected to occur after repeated oral dosing. However, in this current study, the PK properties of esomeprazole in Beagles were slightly different from those observed in human studies.…”

Section: Discussionmentioning

confidence: 99%

“…Previous study to evaluate efficacy of oral omeprazole reported that the MPT with pH ≥4 was 52 ± 17% and 44 ± 18% after treatment with an omeprazole tablet (1.5–2.6 mg/kg q24 hours) and a reformulated omeprazole paste (1.5–2.6 mg/kg q24 hours), respectively 1. The AUC of esomeprazole in people has been reported to be higher than that of omeprazole of the same dose 3. The efficacy of esomeprazole in suppressing gastric acid is closely related to the subject's total exposure to the drug (ie, the AUC), and for that reason, esomeprazole has been shown to result in better acid suppression than omeprazole of equal doses in human studies 3, 5, 6, 25, 26.…”

Section: Discussionmentioning

confidence: 99%

“…Esomeprazole was developed as the first single optical PPI (2000, AstraZeneca) containing only S‐isomer of omeprazole, the R‐isomer being absent 3. Esomeprazole provides better acid control and more favorable pharmacokinetics (PKs) relative to currently used racemic PPIs in human 4, 5, 6.…”

mentioning

confidence: 99%

“…Esomeprazole provides better acid control and more favorable pharmacokinetics (PKs) relative to currently used racemic PPIs in human 4, 5, 6. Treatment with a single oral dose of esomeprazole resulted in a greater total area under the plasma concentration‐time curve (AUC) and a more rapid increase in gastric pH than the same dose of racemic omeprazole 3, 6. In 8‐week clinical trials involving patients with erosive esophagitis, the treatment group receiving esomeprazole showed significantly higher healing rates than patients receiving omeprazole or lansoprazole 4.…”

mentioning

confidence: 99%

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Pharmacokinetics and Acid Suppressant Efficacy of Esomeprazole after Intravenous, Oral, and Subcutaneous Administration to Healthy Beagle Dogs

Hwang

Jeong

Song

et al. 2017

Veterinary Internal Medicne

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BackgroundEsomeprazole is an S‐enantiomer of omeprazole that has favorable pharmacokinetics and efficacious acid suppressant properties in humans. However, the pharmacokinetics and effects on intragastric pH of esomeprazole in dogs have not been reported.ObjectiveTo determine the pharmacokinetics of esomeprazole administered via various routes (PK study) and to investigate the effect of esomeprazole on intragastric pH with a Bravo pH monitoring system (PD study).AnimalsSeven adult male Beagle dogs and 5 adult male Beagle dogs were used for PK and PD study, respectively.MethodsBoth studies used an open, randomized, and crossover design. In the PK study, 7 dogs received intravenous (IV), subcutaneous (SC), and oral doses (PO) of esomeprazole (1 mg/kg). Each treatment period was separated by a washout period of at least 10 days. Esomeprazole plasma concentrations were measured by HPLC/MS/MS. In the efficacy study, intragastric pH was recorded without medication (baseline pH) and following IV, SC, and PO esomeprazole dosing regimens (1 mg/kg) in 5 dogs.ResultsThe bioavailability of esomeprazole administered as PO enteric‐coated granules and as SC injections was 71.4 and 106%, respectively. The half‐life was approximately 1 hour. Mean ± SD percent time intragastric pH was ≥3 and ≥4 was 58.9 ± 21.1% and 40.9 ± 17.3% for IV group, 75.8 ± 16.4% and 62.7 ± 17.7% for SC group, 88.2 ± 8.9% and 82.5 ± 7.7% for PO group, and 12.5 ± 3.6% and 3.7 ± 1.8% for baseline. The mean percent time with intragastric pH was ≥3 or ≥4 was significantly increased regardless of the dosing route (P < .05).ConclusionThe PK parameters for PO and SC esomeprazole administration were favorable, and esomeprazole significantly increased intragastric pH after IV, PO, and SC administration. IV and SC administration of esomeprazole might be useful when PO administration is not possible. No significant adverse effects were observed.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%